Behavioral & Pharmacological Analysis of Drugs of Abuse

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• 批准号: 6515364
• 负责人: JERROLD Clyne WINTER
• 金额: $ 35.1万
• 依托单位: STATE UNIVERSITY OF NEW YORK AT BUFFALO
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-01-01 至 2006-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6515364
• 关键词: 2,5 dimethoxy 4 methylamphetamine; NMDA receptors; autoradiography; clozapine; drug abuse; drug interactions; drug receptors; gas chromatography mass spectrometry; glutamate receptor; glutamates; inhibitor /antagonist; laboratory rat; lysergic acid diethylamide; neuropharmacology; psychopharmacology; receptor expression; serotonin; serotonin inhibitor; substance abuse related behavior

The discovery by Albert Hofmann more than fifty years ago of the hallucinogenic effects of LSD irreversibly altered the course of both biological psychiatry and popular culture. Hallucinogens of all types are subject to widespread and increasing abuse by adolescents and young adults in this country. For example, in 1998 use of hallucinogens exceeded that of cocaine in the age groups 12-17 and 18-25. Indeed, hallucinogens were more commonly ingested than tranquilizers, inhalants, and sedatives combined. Furthermore, LSD was identified in 1999 as a "club drug" in the campaign by the National Institute on Drug Abuse to alert the public to the hazards of these agents. In addition to the well recognized abuse liability of these drugs, hallucinogens are perhaps unique in that an understanding of their mechanisms of action would contribute not only to an amelioration of the burdens of illicit use but might also provide a key to solving the puzzle of psychosis, another major human affliction. The present investigations seek to characterize indoleamine hallucinogens such as LSD and phenethylamine hallucinogens as exemplified by DOM in combined behavioral, biochemical, and analytical [GC-MS] studies. Specifically, studies will also examine the neuroanatomical sites involved in hallucinogen- induced stimulus control. In addition, experiments will further characterize interactions between the serotonergic and glutamatergic systems in the brain. Finally, the mechanisms responsible for the potentiation of LSD and other hallucinogens by fluoxetine and related selective serotonin reuptake inhibitors will be examined. Taken together, the correlational use of powerful methods for the assessment of in vivo and in vitro efficacy and of brain levels of DOM and of neurotransmitters will provide new understanding of the mode of action of hallucinogens.

50多年前，阿尔伯特·霍夫曼发现了LSD的致幻作用，这一发现不可逆转地改变了生物精神病学和流行文化的进程。在这个国家，所有类型的迷幻剂都会受到青少年和年轻人的广泛和日益增加的滥用。例如，1998年，在12-17岁和18-25岁年龄组中，迷幻剂的使用量超过了可卡因。事实上，迷幻剂的摄入量比镇静剂、吸入剂和镇静剂的总和还要普遍。此外，1999年，在国家药物滥用研究所开展的提醒公众注意这些制剂的危险的运动中，LSD被确定为“俱乐部毒品”。除了公认的这些药物的滥用责任外，致幻剂可能是独一无二的，因为了解它们的作用机制不仅有助于减轻非法使用的负担，还可能为解决精神错乱这一人类另一大痛苦提供一把钥匙。目前的研究试图表征吲哚胺类致幻剂，如LSD和苯乙胺致幻剂，如DOM在联合行为、生化和分析[GC-MS]研究中的例证。具体地说，研究还将检查与迷幻剂诱导的刺激控制有关的神经解剖部位。此外，实验将进一步描述大脑中5-羟色胺能系统和谷氨酸能系统之间的相互作用。最后，我们将探讨氟西汀和相关的选择性5-羟色胺再摄取抑制剂增强LSD和其他致幻剂的作用机制。综上所述，相关使用强大的方法来评估体内和体外的疗效以及DOM和神经递质的脑水平将提供对迷幻剂作用模式的新理解。